Phenylaminopyrimidine-Derived Compounds, Method for Obtaining, Using Said Compounds in the Treatment of Cancer, and Treatment Methods

Abstract

The present invention relates to novel phenylaminopyrimidine(FAP)-derived compounds of general formulas I and II: Where, in formula I, R 1 is: Where, in formula II, X + is selected among one of the compounds below: Where, in formula II, Y is The compounds of the present invention are powerful and nonspecific tyrosine kinase inhibitors, and the use of these compounds in the treatment.

1 . A compound derived from phenylaminopyrimidine selected from the group consisting of formula I and formula II: 
       
         
           
           
               
               
           
         
         wherein, in formula I, R 1  is 
       
       
         
           
           
               
               
           
         
       
       and
 wherein, in formula II, X +  is selected from the group consisting of: 
 
       
         
           
           
               
               
           
         
         and wherein Y −  is: 
       
       
         
           
           
               
               
           
         
       
     
     
         2 . The compound of  claim 1 , wherein the compound is of formula I and is:
 (3R,5aS,6R,8aS,9R,10R,12R,12aR)-3,6,9-trimethyldecahydro-3H-3-,12-epoxy[1,2]dioxopyne[4,3-yl]isochromen10-yl-4-((4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)amino)-4-oxobutanoate.   
     
     
         3 . The compound of  claim 1 , wherein the compounds is of formula II and is selected from the group consisting of:
 N-(2-methyl-5-(4-((4-methylpiperazine-1-yl)methyl)benzamide)phenyl)-4-(pyridin-3-yl)pyrimidin-2-aminium-4-oxo-4-(((3R,5aS,6R,8aS,9R,10R,12R,12aR)-3,6,9-trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepin[4,3-yl]isochromen-10-yl)oxy)butanoate   and 4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzenaminium-4-oxo-4-(((3R,5aS,6R,8aS,9R,10R,12R,12aR)-3,6,9-trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepin[4,3-yl]isochromen-10-yl)oxy)butanoate.   
     
     
         4 . A process for preparing a compound of formula I, as defined in  claim 1 , comprising a single step of stirring a mixture of artesunic acid and phenylaminopyrimidine in the presence of a coupling agent, at room temperature for 24 hours. 
     
     
         5 . The process of  claim 4 , wherein the coupling agent is 1-hydroxybenzotriazole hydrate (EDC) and 1-ethyl-3(3-dimethylaminopropyl)carbodiimide) (HOBT). 
     
     
         6 . A process for preparing a compound of formula II, as defined in  claim 1 , comprising a single step of reacting artesunic acid and one base selected from the group consisting of imatinib and phenylaminopyrimidine in the presence of an alcohol, under stirring, at room temperature for 24 hours. 
     
     
         7 . The process, according to  claim 6 , wherein the alcohol is methanol. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . A pharmaceutical composition comprising a compound of  claim 1 . 
     
     
         11 . A method of treating chronic myelogenous leukemia comprising administering the pharmaceutical composition of  claim 10 . 
     
     
         12 . A method for treating cancer comprising administering a therapeutically effective amount of at least one compound of formulas I or formula II, as defined in  claim 1 . 
     
     
         13 . The method of  claim 12 , wherein the cancer is chronic myelogenous leukemia. 
     
     
         14 . The method of  claim 12 , comprising inhibiting tyrosine kinase enzyme. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 12 , comprising inducing apoptosis of cancerous cells.